Recurrent staphylococcal scalded skin syndrome in a 20‐month old—A case report

Key Clinical Message We present a case of a 20‐month‐old child with a history of atopic dermatitis that exhibited recurrent erythematous‐bullous lesions consistent with Staphylococcal Scalded Skin syndrome (SSSS). SSSS is an exfoliative toxin‐mediated skin disorder most commonly found in children. In this paper, we discuss the importance of recognizing the clinical symptomatology and progressive nature of SSSS, particularly in patients with a history of atopic dermatitis, to ensure prompt treatment and resolution of the syndrome.


| BACKGROUND
Staphylococcal Scalded Skin Syndrome (SSSS) is an exfoliative skin disease usually due to a toxin produced by a Staphylococcus aureus infection. 1 Toxin a or b from S. aureus spread hematogenously and have been shown to lyse the cell-cell adhesion molecule desmoglein-1 in the superficial epidermis, causing intraepidermal splitting and thus a loss of structural integrity. 2 SSSS primarily occurs in children and neonates and is rare in adults. [3][4][5] We present a case of a 20-month-old patient who presented with progressive SSSS and recurrence of SSSS to emphasize the role of early treatment and diagnosis in reducing the morbidity of the disease.

| Initial admission
Day 1: A 19-month-old African American male presented to the emergency department (ED) with erythematous patches and blistering on his face and neck as well as erythematous patches on his buttocks ( Figure 1). Patient had a history of atopic dermatitis primarily affecting bilateral antecubital fossa managed with triamcinolone acetonide 0.1% cream as needed for up to 2 weeks. The patient had no new medications prior to this event and was up to date on relevant immunizations.
Per caregivers who were present at ED, the patient was also irritable, had reduced appetite, and appeared fatigued 3-5 days before presentation. The patient also experienced 2 days of afebrile dry cough, rhinorrhea, and sinus congestion, increased scratching of the antecubital fossa due to his atopic dermatitis. Upon rubbing of the perinasal and perioral area in the ED, the uppermost layer of skin sloughed off with minimal pressure (positive Nikolsky's sign). On physical exam, erythema and edema were present. The mucous membranes of the mouth and pharynx were not affected. The patient was apyretic. The patient's initial white blood cell count (WBC) was 8.3 × 10^9/L. We obtained blood and ear mucosal wound cultures for further investigation. A diagnosis of SSSS was made based on history and clinical features. The diagnoses of bullous

Key Clinical Message
We present a case of a 20-month-old child with a history of atopic dermatitis that exhibited recurrent erythematous-bullous lesions consistent with Staphylococcal Scalded Skin syndrome (SSSS). SSSS is an exfoliative toxin-mediated skin disorder most commonly found in children. In this paper, we discuss the importance of recognizing the clinical symptomatology and progressive nature of SSSS, particularly in patients with a history of atopic dermatitis, to ensure prompt treatment and resolution of the syndrome.

K E Y W O R D S
atopic dermatitis, exotoxins, staph scalded skin syndrome, staphylococcus, toxic epidermal necrolysis impetigo and toxic epidermal necrolysis (TEN) were also considered, but the lack of mucous membrane involvement in our patient made SSSS more likely. A skin biopsy was not performed as the clinical presentation was consistent with SSSS.
The patient received IV nafcillin 40 mg/kg/day every 6 h after admission as well as intravenous fluids. For pain control, the patient was given ibuprofen and acetaminophen as needed. The patient's wounds were covered with sterile bandages. Days 2-3: After discussion with the caregivers, on day 2 the patient was started on IV clindamycin 30 mg/kg/day to target the exfoliative toxin of S. aureus. After 48 h, the results of the blood and ear mucosal wound cultures were negative, and the urine analysis was clear. The patient's pain was controlled. However, the patient's caregivers noticed increased periorbital edema without drainage on day 2. The edema was thought to be due to third spacing in the setting of inflammation, and fluids were decreased to keep vein open (KVO).
Of note, the patient's WBC count of 5.0 × 10^9 /L (ANC 0.9) on hospital day 3 was thought to be caused by IV nafcillin. Repeat complete blood count (CBC) within 24 h showed WBC count of 5.1 (absolute neutrophil count, ANC, 1.2). On day 3, periorbital edema was decreased, and skin lesions were healing with crusting ( Figure 2). The patient was taking adequate oral intake, and the IV antibiotics were transitioned to oral cephalexin, and clindamycin was discontinued. The patient was discharged on an appropriate 7-day course of oral cephalexin, topical mupirocin, and close outpatient pediatric follow-up.
Readmission, 3 weeks later: Subsequently, the now 20-month-old patient presented to the ED with erythematous patches on face, neck, hyperpigmentation on buttocks consistent with SSSS. Patient's caregivers stated that patient's skin was clear for 2 weeks after initial admission and treatment, and the patient continued to scratch antecubital fossa at night due to atopic dermatitis. The patient's mother noticed an erythematous patch behind the ear, which had worsened over the past 2 days, so she brought the patient to the ED. At readmission, there was also no involvement of mucosal membranes and thus no concern for Steven's Johnson Syndrome (SJS). CBC and complete metabolic panel (CMP) were obtained in the ED and were in the normal range except for a low Na, 133 mmol/L. Blood cultures were obtained, showing no growth after 48 h; wound cultures identified no organisms. Initially, the patient was given IV nafcillin for Methicillin-sensitive Staphylococcus aureus (MSSA) coverage because, during the prior admission, this treatment healed the rash.  After discussion with the Pediatric Infectious Disease team, on day 2 the patient was switched from IV nafcillin to a 10 day course of PO Linezolid. The Pediatrics ID team was concerned that, due to the rapid recurrence of SSSS, this patient may be experiencing a rare case of Methicillinresistant Staphylococcus aureus (MRSA) caused SSSS. Thus, the coverage needed to be broadened.
On day 3, the patient had fewer new lesions, and previous lesions appeared to be healing with scabbing and hyperpigmentation. He was afebrile during his entire hospital stay. The patient was also well appearing with adequate by mouth (PO) intake during the hospital stay and was discharged on day 3 with close outpatient pediatric follow up. The patient's mother was appropriately concerned about immune deficiency, given the recurrence of SSSS. Pediatrics Infectious Disease commented that his readmission was more likely due to MRSA rather than MSSA, which is why SSSS recurred. The patient was also otherwise a normally developing child with excellent growth. The patient's mother knew she needed to return should symptoms worsen or reoccur.

| DISCUSSION
In this case report, the prompt diagnosis and treatment of SSSS during the first ED admission allowed the patient to heal, and the subsequent readmission with broadened antibiotic coverage allowed for timely discharge and effective treatment.
SSSS, or Ritter's disease, is a rare disease process that typically occurs in children. The preceding S. aureus infection spreads in the bloodstream and lyses the desmoglein-1 proteins in the stratum granulosum layer of the epidermis. 1,2,6 This separation of the anchoring desmosomes leads to the exfoliative presentation of SSSS. SSSS typically arises from an area of infection, such as impetigo, bacterial conjunctivitis, or iatrogenic wounds. 7 The susceptibility of children, particularly neonates, to the acquisition of SSSS has been postulated to result from the lack of protective antibodies to S. aureus toxins and/ or the insufficient excretion of exotoxins from children's kidneys. 1 The diagnosis of SSSS is mainly clinical. Prodromal symptoms of irritability, skin pain, fever, and poor feeding are common. Cutaneous erythema may initially present in the skin folds of the neck, axillae, and gluteal region before becoming generalized within the first 48 hours of presentation. 7 On exam, the skin may have flaccid bullae that erode upon minimal pressure. Additionally, superficial desquamation occurs due to the exotoxin's lytic mechanism. 6 There is typically a quick progression of the disease process.
The standard treatment of SSSS includes IV antibiotics against staphylococcal species (e.g., Nafcillin, oxacillin) and supportive care. [6][7][8][9] Empiric treatment with penicillinase-resistant penicillins is done initially, with broadening for MRSA coverage considered when clinical improvement is not observed or in communities with high MRSA incidence. 10 In our case, MRSA coverage (PO linezolid) was added after initial clearing and improvement was followed by a recurrence of SSSS. Clarithromycin can be given to patients with a penicillin allergy. 8 Other therapies, such as IV immunoglobulin, have been suggested to antagonize the exfoliative toxins of SSSS. 11 Patients may continue to have skin pain following treatment as well as post-inflammatory hypopigmentation or hyperpigmentation during the healing process. 6 SSSS risks progressing to sepsis if not recognized and treated early. Other complications include secondary infection, dehydration, electrolyte imbalance, and death. 5,12 Recurrent SSSS in the pediatric population is rare, and a literature review revealed recurrent SSSS documented more often in the neonate population than in infants or older pediatric patients. Specifically, five reported cases occurred in neonates in either healthy full-term, preterm, or low birth-weight neonates. [13][14][15][16][17] One of these case reports details two Taiwanese siblings with Netherton syndrome, a condition that impairs skin barrier protection, and immune response. 17 We found one case report of two children in Tanzania, aged 5 and 10, with recurrent SSSS. 18 Our 20-month-old pediatric patient is a unique case of recurrent SSSS in a toddler-aged patient.
The differential diagnosis for SSSS includes TEN and SJS. 5 TEN and SJS have mucous membrane and cutaneous involvement, which was absent here. Bullous impetigo is also on the differential diagnosis, but bullous impetigo has localized skin infection rather than hematogenous spread. The former has more limited involvement and a less severe clinical presentation. 6

| CONCLUSION
This case report highlights the importance of prompt evaluation and antibiotic treatment as well as the consideration of MRSA in SSSS. More research is necessary to elucidate the prevalence and resistant staphylococcal strains and therapies for SSSS caused by MRSA. This case report aims to support research in exfoliative skin conditions further.

FUNDING INFORMATION
None.